All publications herein are incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference. The following description includes information that may be useful in understanding the present invention. It is not an admission that any of the information provided herein is prior art or relevant to the presently claimed invention, or that any publication specifically or implicitly referenced is prior art.
A stem cell is a cell type that has a unique capacity to renew itself and give rise to specialized or differentiated cells. Although most cells of the body are committed to conduct a specific function, a stem cell is uncommitted, until it receives a signal to develop into a specialized cell type. What makes the stem cells unique is their proliferative capacity, combined with their ability to become specialized. Somatic stem cells are present in the adult organism. Pluripotency tests have shown that whereas the embryonic or blastocyst-derived stem cells can give rise to all cells in the organism, including the germ cells, somatic stem cells have a more limited repertoire in descendent cell types.
To date, some studies have shown that human embryonic stem (“ES”) cells can be induced to differentiate into cells with gene expression profiles characteristic of hepatocytes on a modest scale. However, there remains a need in the art for novel methods of actually inducing liver stem or progenitor cells from human ES cell culture. Large scale production of hepatocyte precursors from human ES cells has application in several key areas; for example, to enable in vitro studies of the pathogenesis of liver disease, such as viral hepatitis; to enable studies of the metabolism and toxicity of drugs in vitro, leading to better predictive toxicology tests; and to provide cells for transplantation therapy in liver diseases such as Hepatitis C, which is currently a worldwide epidemic affecting over 200 million patients.
Thus, there is a need in the art for novel methods of inducing liver progenitor cells from stem cells.